Denosumab Therapy Appears to Improve Bone Strength

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.